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Short-term outcomes of deceased donor renal transplants of HCV uninfected recipients from HCV seropositive nonviremic donors and viremic donors in the era of direct-acting antivirals.

ABSTRACT: The United States opioid use epidemic over the past decade has coincided with an increase in hepatitis C virus (HCV) positive donors. Using propensity score matching, and the Organ Procurement Transplant Network data files from January 2015 to June 2019, we analyzed the short-term outcomes of adult deceased donor kidney transplants of HCV uninfected recipients with two distinct groups of HCV positive donors (HCV seropositive, nonviremic n = 352 and viremic n = 196) compared to those performed using HCV uninfected donors (n = 36 934). Compared to the reference group, the transplants performed using HCV seropositive, nonviremic and viremic donors experienced a lower proportion of delayed graft function (35.2 vs 18.9%; P < .001 [HCV seropositive, nonviremic donors] and 36.2 vs 16.8% ; P < .001[HCV viremic donors]). The recipients of HCV viremic donors had better allograft function at 6 months posttransplant (eGFR [54.1 vs 68.3 mL/min/1.73 m2; P = .004]. Furthermore, there was no statistical difference in the overall graft failure risk at 12 months posttransplant by propensity score matched multivariable Cox proportional analysis (HR = 0.60, 95% CI 0.23 to 1.29 [HCV seropositive, nonviremic donors] and HR = 0.85, 95% CI 0.25 to 2.96 [HCV viremic donors]). Further studies are required to determine the long-term outcomes of these transplants and address unanswered questions regarding the use of HCV viremic donors.

SUBMITTER: La Hoz RM

PROVIDER: S-EPMC6864234 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Short-term outcomes of deceased donor renal transplants of HCV uninfected recipients from HCV seropositive nonviremic donors and viremic donors in the era of direct-acting antivirals.

La Hoz Ricardo M RM Sandıkçı Burhaneddin B Ariyamuthu Venkatesh K VK Tanriover Bekir B

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20190807 11

The United States opioid use epidemic over the past decade has coincided with an increase in hepatitis C virus (HCV) positive donors. Using propensity score matching, and the Organ Procurement Transplant Network data files from January 2015 to June 2019, we analyzed the short-term outcomes of adult deceased donor kidney transplants of HCV uninfected recipients with two distinct groups of HCV positive donors (HCV seropositive, nonviremic n = 352 and viremic n = 196) compared to those performed u ...[more]

PMID: 31207073

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Project description:BackgroundHearts and lungs from donors with hepatitis C viremia are typically not transplanted. The advent of direct-acting antiviral agents to treat hepatitis C virus (HCV) infection has raised the possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection.MethodsWe conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV infection. Sofosbuvir-velpatasvir, a pangenotypic direct-acting antiviral regimen, was preemptively administered to the organ recipients for 4 weeks, beginning within a few hours after transplantation, to block viral replication. The primary outcome was a composite of a sustained virologic response at 12 weeks after completion of antiviral therapy for HCV infection and graft survival at 6 months after transplantation.ResultsA total of 44 patients were enrolled: 36 received lung transplants and 8 received heart transplants. The median viral load in the HCV-infected donors was 890,000 IU per milliliter (interquartile range, 276,000 to 4.63 million). The HCV genotypes were genotype 1 (in 61% of the donors), genotype 2 (in 17%), genotype 3 (in 17%), and indeterminate (in 5%). A total of 42 of 44 recipients (95%) had a detectable hepatitis C viral load immediately after transplantation, with a median of 1800 IU per milliliter (interquartile range, 800 to 6180). Of the first 35 patients enrolled who had completed 6 months of follow-up, all 35 patients (100%; exact 95% confidence interval, 90 to 100) were alive and had excellent graft function and an undetectable hepatitis C viral load at 6 months after transplantation; the viral load became undetectable by approximately 2 weeks after transplantation, and it subsequently remained undetectable in all patients. No treatment-related serious adverse events were identified. More cases of acute cellular rejection for which treatment was indicated occurred in the HCV-infected lung-transplant recipients than in a cohort of patients who received lung transplants from donors who did not have HCV infection. This difference was not significant after adjustment for possible confounders.ConclusionsIn patients without HCV infection who received a heart or lung transplant from donors with hepatitis C viremia, treatment with an antiviral regimen for 4 weeks, initiated within a few hours after transplantation, prevented the establishment of HCV infection. (Funded by the Mendez National Institute of Transplantation Foundation and others; DONATE HCV ClinicalTrials.gov number, NCT03086044.).

Project description:BACKGROUND AND OBJECTIVES:The fraction of kidneys procured for transplant that are discarded is rising in the United States. Identifying donors from whom only one kidney was discarded allows us to control for donor traits and better assess reasons for organ discard. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We conducted a retrospective cohort study using United Network for Organ Sharing Standard Transplant Analysis and Research file data to identify deceased donors from whom two kidneys were procured and at least one was transplanted. Unilateral pairs were defined as kidney pairs from a single donor from whom one kidney was discarded ("unilateral discard") but the other was transplanted ("unilateral transplant"). Organ quality was estimated using the Kidney Donor Risk Index and Kidney Donor Profile Index (KDPI). We compared all-cause graft failure rates for unilateral transplants to those for bilateral transplant Kaplan-Meier methods, and life table methodology was used to evaluate 1-, 2-, 3-, and 5-year survival rates of transplants from bilateral and unilateral donors. RESULTS:Compared with bilateral donors (i.e., both kidneys transplanted) (n=80,584), unilateral donors (i.e., only one kidney transplanted) (n=7625) had higher mean terminal creatinine (1.3±2.1 mg/dl versus 1.1±0.9 mg/dl) and KDPI (67%±25% versus 42%±27%), were older, and were more likely to have hypertension, diabetes, hepatitis C, terminal stroke, or meet Centers for Disease Control and Prevention high-risk donor criteria. Unilateral discards were primarily attributed to factors expected to be similar in both kidneys from a donor: biopsy findings (22%), no interested recipient (13%), and donor history (7%). Anatomic abnormalities (14%), organ damage (11%), and extended ischemia (6%) accounted for about 30% of discards, but were the commonest reasons among low KDPI kidneys. Among kidneys with KDPI?60%, there was an incremental difference in allograft survival over time (for unilateral versus bilateral transplants, 1-year survival: 83% versus 87%; 3-year survival: 69% versus 73%; 5-year survival: 51% versus 58%). CONCLUSIONS:A large number of discarded kidneys were procured from donors whose contralateral kidneys were transplanted with good post-transplant outcomes.

Project description:Introduction. While use of (hepatitis C virus) HCV-viremic kidneys may result in net benefit for the average end-stage kidney disease (ESKD) patient awaiting transplantation, patients may have different values for ESKD-related health states. Thus, the best decision for any individual may be different depending on the balance of these factors. Our objective was to explore the feasibility of sampling health utilities from hemodialysis patients in order to perform patient-specific decision analyses considering various transplantation strategies. Study Design. We assessed utilities on a convenience sample of hemodialysis patients for health states including hemodialysis, and transplantation with either an HCV-uninfected kidney or an HCV-viremic kidney. We performed patient-specific decision analyses using each patient's age, race, gender, dialysis vintage, and utilities. We used a Markov state transition model considering strategies of continuing hemodialysis, transplantation with an HCV-unexposed kidney, and transplantation with an HCV-viremic kidney and HCV treatment. We interviewed 63 ESKD patients from four dialysis centers (Dialysis Clinic Inc., DCI) in the Cincinnati metropolitan area. Results. Utilities for ESKD-related health states varied widely from patient to patient. Mean values were highest for -transplantation with an HCV-uninfected kidney (0.89, SD: 0.18), and were 0.825 (SD: 0.231) and 0.755 (SD: 0.282), respectively, for hemodialysis and transplantation with an HCV-viremic kidney. Patient-specific decision analyses indicated 37 (59%) of the 63 ESKD patients in the cohort would have a net gain in quality-adjusted life years from transplantation of an HCV-viremic kidney, while 26 would have a net loss. Conclusions. It is feasible to gather dialysis patients' health state utilities and perform personalized decision analyses. This approach could be used in the future to guide shared decision-making discussions about transplantation strategies for ESKD patients.

Project description:Purpose of programThe ongoing shortage of organs for transplant combined with Manitoba having the highest prevalence of end-stage renal disease (ESRD) in Canada has resulted in long wait times on the deceased donor waitlist. Therefore, the Transplant Manitoba Adult Kidney Program has ongoing quality improvement initiatives to expand the deceased donor pool. This clinical transplant protocol describes the use of prophylactic pan-genotypic direct-acting anti-viral agents (DAA) for transplanting hepatitis C (HCV)-viremic kidneys (HCV antibody positive/nucleic acid [nucleic acid amplification testing, NAT] positive) to HCV-naïve recipients as routine standard of care. We will evaluate the provincial implementation of this protocol as a prospective observational cohort study.Sources of informationScoping literature review and key stakeholder engagement with interdisciplinary health care providers and health system leaders/decision markers.MethodsPatients will be screened pre-transplant for eligibility and undergo a multilevel education and consent process to participate in this expanded donor program. Incident adult HCV-naïve recipients of an HCV-viremic kidney transplant will be treated prophylactically with glecaprevir-pibrentasvir with the first dose administered on call to the operation. Glecaprevir-pibrentasvir will be used for 8 weeks with viral monitoring and hepatology follow-up. Primary outcomes are sustained virologic response (SVR) at 12 weeks and the tolerability of DAA therapy. Secondary outcomes within the first year post-transplant are patient and graft survival, graft function, biopsy-proven rejection, HCV transmission to recipient (HCV NAT positive), and HCV nonstructural protein 5A (NS5A) resistance. Safety outcomes within the first year post-transplant include fibrosing cholestatic hepatitis, acute liver failure, primary and secondary DAA treatment failure, HCV transmission to a recipient's partner, elevated liver enzymes ≥2-fold, abnormal international normalized ratio (INR), angioedema, anaphylaxis, cirrhosis, and hepatocellular carcinoma.Key findingsThis program successfully advocated for and obtained hospital formulary, provincial Exceptional Drug Status (EDS), and Non-Insured Health Benefits (NIHB) to provide prophylactic DAA therapy for this indication, and this information may be useful to other provincial transplant organizations seeking to establish an HCV-viremic kidney transplant program with prophylactic DAA drug coverage.Limitations(1) Patient engagement was not undertaken during the program design phase, but patient-reported experience measures will be obtained for continuous quality improvement. (2) Only standard criteria donors (optimal kidney donor profile index [KDPI] ≤60) will be used. If this approach is safe and feasible, then higher KDPI donors may be included.ImplicationsThe goal of this quality improvement project is to improve access to kidney transplantation for Manitobans. This program will provide prophylactic DAA therapy for HCV-viremic kidney transplant to HCV-naïve recipients as routine standard of care outside a clinical trial protocol. We anticipate this program will be a safe and effective way to expand kidney transplantation from a previously unutilized donor pool.

Project description:Background and objectivesData reported to the Organ Procurement and Transplantation Network (OPTN) are used in kidney transplant research, policy development, and assessment of center quality, but the accuracy of early post-transplant outcome measures is unknown.Design, setting, participants, & measurementsThe Deceased Donor Study (DDS) is a prospective cohort study at five transplant centers. Research coordinators manually abstracted data from electronic records for 557 adults who underwent deceased donor kidney transplantation between April of 2010 and November of 2013. We compared the post-transplant outcomes of delayed graft function (DGF; defined as dialysis in the first post-transplant week), acute rejection, and post-transplant serum creatinine reported to the OPTN with data collected for the DDS.ResultsMedian kidney donor risk index was 1.22 (interquartile range [IQR], 0.97-1.53). Median recipient age was 55 (IQR, 46-63) years old, 63% were men, and 47% were black; 93% had received dialysis before transplant. Using DDS data as the gold standard, we found that pretransplant dialysis was not reported to the OPTN in only 11 (2%) instances. DGF in OPTN data had a sensitivity of 89% (95% confidence interval [95% CI], 84% to 93%) and specificity of 98% (95% CI, 96% to 99%). Surprisingly, the OPTN data accurately identified acute allograft rejection in only 20 of 47 instances (n=488; sensitivity of 43%; 95% CI, 17% to 73%). Across participating centers, sensitivity of acute rejection varied widely from 23% to 100%, whereas specificity was uniformly high (92%-100%). Six-month serum creatinine values in DDS and OPTN data had high concordance (n=490; Lin concordance correlation =0.90; 95% CI, 0.88 to 0.92).ConclusionsOPTN outcomes for recipients of deceased donor kidney transplants have high validity for DGF and 6-month allograft function but lack sensitivity in detecting rejection. Future studies using OPTN data may consider focusing on allograft function at 6 months as a useful outcome.

Project description:ImportanceCancer transmission is a known risk for recipients of organ transplants. Many people wait a long time for a suitable transplant; some never receive one. Although patients with brain tumors may donate their organs, opinions vary on the risks involved.ObjectiveTo determine the risk of cancer transmission associated with organ transplants from deceased donors with primary brain tumors. Key secondary objectives were to investigate the association that donor brain tumors have with organ usage and posttransplant survival.Design, setting, and participantsThis was a cohort study in England and Scotland, conducted from January 1, 2000, to December 31, 2016, with follow-up to December 31, 2020. This study used linked data on deceased donors and solid organ transplant recipients with valid national patient identifier numbers from the UK Transplant Registry, the National Cancer Registration and Analysis Service (England), and the Scottish Cancer Registry. For secondary analyses, comparators were matched on factors that may influence the likelihood of organ usage or transplant failure. Statistical analysis of study data took place from October 1, 2021, to May 31, 2022.ExposuresA history of primary brain tumor in the organ donor, identified from all 3 data sources using disease codes.Main outcomes and measuresTransmission of brain tumor from the organ donor into the transplant recipient. Secondary outcomes were organ utilization (ie, transplant of an offered organ) and survival of kidney, liver, heart, and lung transplants and their recipients. Key covariates in donors with brain tumors were tumor grade and treatment history.ResultsThis study included a total of 282 donors (median [IQR] age, 42 [33-54] years; 154 females [55%]) with primary brain tumors and 887 transplants from them, 778 (88%) of which were analyzed for the primary outcome. There were 262 transplants from donors with high-grade tumors and 494 from donors with prior neurosurgical intervention or radiotherapy. Median (IQR) recipient age was 48 (35-58) years, and 476 (61%) were male. Among 83 posttransplant malignancies (excluding NMSC) that occurred over a median (IQR) of 6 (3-9) years in 79 recipients of transplants from donors with brain tumors, none were of a histological type matching the donor brain tumor. Transplant survival was equivalent to that of matched controls. Kidney, liver, and lung utilization were lower in donors with high-grade brain tumors compared with matched controls.Conclusions and relevanceResults of this cohort study suggest that the risk of cancer transmission in transplants from deceased donors with primary brain tumors was lower than previously thought, even in the context of donors that are considered as higher risk. Long-term transplant outcomes are favorable. These results suggest that it may be possible to safely expand organ usage from this donor group.

Dataset Information

Short-term outcomes of deceased donor renal transplants of HCV uninfected recipients from HCV seropositive nonviremic donors and viremic donors in the era of direct-acting antivirals.

Publications

Short-term outcomes of deceased donor renal transplants of HCV uninfected recipients from HCV seropositive nonviremic donors and viremic donors in the era of direct-acting antivirals.

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